This research proposes to elucidate the mechanisms by which a unique group of enzymes inactivate eukaryotic ribosomes. These studies are centered upon the antiviral protein from Phytolacca americana (PAP) which is known to specifically inhibit polypeptide chain elongation by causing an unknown enzymatic modification of the 60S ribosomal subunit. A major objective of this research is to determine the sites of action of PAP and other ribosome specific enzymes upon the 60S ribosomal subunit. This determination will require the careful analysis of the ribosomal RNA and proteins obtained from the 60S subunit of a number of different eukaryotic ribosomes treated with PAP and other ribosome specific enzymes. The analysis will be accomplished by polyacrylamide gel electrophoresis of ribosomal components differentially labelled with isotopes to distinguish control and treated species. These studies are to be complemented by the purification and characterization of other enzymes which will enzymatically inactivate ribosomes. The final goal of this proposal is to determine the mechanism by which PAP blocks viral transmission by studying the action of this protein upon virus infection of mammalian cells.